Graves OphthalmopathyLYMPHGONCT03195296
T and B Cells in Graves' Orbitopathy
An observational study of Graves Ophthalmopathy, run by University of Pisa.
Trial summary
Graves orbitopathy (GO) is an inflammatory eye disease associated in 95% of patients with Graves' hyperthyroidism (GH), in ~3-4% with hypothyroid autoimmune thyroiditis, and in ~1-2% with thyroid autoimmunity in the absence of thyroid dysfunction, the former known as euthyroid GO. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Graves Ophthalmopathy
- How many people
- 20 participants
- Where
- No sites listed yet
- Study dates
- 1 Jan 2017to 31 May 2017
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Consecutive patients with Graves' orbitopathy to undergo orbital decompression
Who may be able to join
- Patients with Graves' orbitopathy subjected to orbital decompression
Who cannot join
- None
About this study
Official title: T and B Cells Infiltrating Orbital Tissues in Graves' Orbitopathy (GO) and Their Relation With GO Features
Graves orbitopathy (GO) is an inflammatory eye disease associated in 95% of patients with Graves' hyperthyroidism (GH), in ~3-4% with hypothyroid autoimmune thyroiditis, and in ~1-2% with thyroid autoimmunity in the absence of thyroid dysfunction, the former known as euthyroid GO. The pathogenesis of GO is autoimmune, with the TSH-receptor being considered the major autoantigen, thereby establishing a pathogenetic link between the thyroid and orbital tissue. Thus, TSH-receptor is expressed by orbital fibroblasts, where it forms a complex with the IGF-1 receptor. Unlike GH, which is notoriously caused by TSH-receptor stimulating autoantibodies, GO is believed to reflect cell-mediated autoimmunity, as suggested by studies showing a Th1-like pattern of cytokine release by primary cultures of orbital infiltrating lymphocytes from GO patients. On the other hand, a role of B lymphocytes has emerged in recent years based on the observation that the anti-CD20 monoclonal antibody rituximab has a beneficial effect on GO activity, as demonstrated by a recent randomized clinical trial in which rituximab was compared with intravenous glucocorticoids (GC), being the former the standard treatment of moderately-severe GO. The explanation for the findings was that B lymphocytes are involved in the pathogenesis of GO as antigen-presenting cells. However, in spite of the above mentioned promising observations, another randomized clinical trial in which rituximab was compared with placebo provided opposite results. Thus, rituximab had no effect at all on GO. Data from the two studies were confronted and major differences between the two cohorts emerged, especially concerning GO activity, leading to the conclusion that rituximab may be effective for active, but not for inactive GO. Rituximab has been employed also for autoimmune diseases other than GO, including type 1 diabetes. In the former, it was shown that the effectiveness of rituximab paralleled the presence of CD20-positive infiltrating lymphocytes in pancreas islets. We therefore postulated that something similar may occur in GO, because of which we planned the present, perspective, observational study, aimed at determining the presence and immunohistochemical features of lymphocytes infiltrating orbital tissues in patients with GO and to relate them with the clinical features of GO.
- Conditions
- Graves Ophthalmopathy
- Being tested
- No intervention
- Medical subject headings
- Graves Ophthalmopathy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
No interventionOther
No intervention related to the study is foreseen
| Study group | Role | What they receive |
|---|---|---|
| Graves' Orbitopathy | Patients with Graves' Orbitopathy subjected to orbital decompression Receives: Other: No intervention |
What is being measured
The primary outcome is the main question the study is designed to answer.
Correlation between lymphocytes infiltrating orbital tissue and GO activity
Correlation between the number of lymphocytes infiltrating orbital tissues and the clinical activity score.
The number of infiltrating lymphocytes is the sum of the number counted in four representative fields.
The clinical activity score comprises 7 items (eyelid edema, conjuctival redness, eyelid redness, chemosis, caruncle edema, spontaneous eye pain, gaze-evoked eye pain), resulting in a numerical score going from 1 to 7
Measured: an average of 1 week
Secondary outcomes (2)
Correlation between CD3-positive lymphocytes infiltrating orbital tissue and GO activity
Correlation between the number of CD3-positive lymphocytes infiltrating orbital tissues and the clinical activity score.
The number of CD3 positive infiltrating lymphocytes is the sum of the number counted in four representative fields, following immunohistochemical staining for CD3 The clinical activity score comprises 7 items (eyelid edema, conjuctival redness, eyelid redness, chemosis, caruncle edema, spontaneous eye pain, gaze-evoked eye pain), resulting in a numerical score going from 1 to 7
Measured: an average of 1 week
Correlation between CD20-positive lymphocytes infiltrating orbital tissue and GO activity
Correlation between the number of CD20-positive lymphocytes infiltrating orbital tissues and the clinical activity score.
The number of CD20 positive infiltrating lymphocytes is the sum of the number counted in four representative fields, following immunohistochemical staining for CD20 The clinical activity score comprises 7 items (eyelid edema, conjuctival redness, eyelid redness, chemosis, caruncle edema, spontaneous eye pain, gaze-evoked eye pain), resulting in a numerical score going from 1 to 7
Measured: an average of 1 week
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Jun 2017
- Study start1 Jan 2017
- Primary completion31 May 2017
- Study completion31 May 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Graves OphthalmopathyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case only
- Time perspective
- Prospective
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Pisa
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Marinò Michele, University of Pisa
- Investigators
- Michele Marinò, MD, Principal investigator, University of Pisa
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03195296
- Sponsor's protocol ID
- LYMPHGO
- Acronym
- LYMPHGO
- Status last verified
- Feb 2018
- First submitted
- 19 Jun 2017
- Last updated
- 12 Feb 2018
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 12 Feb 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- T and B Cells Infiltrating Orbital Tissues in Graves' Orbitopathy (GO) and Their Relation With GO Features
- ClinicalTrials.gov ID
- NCT03195296
- Acronym / sponsor ID
- LYMPHGO / LYMPHGO
- Conditions
- Graves Ophthalmopathy
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- University of PisaUniversity, hospital or other
- Study start
- 1 Jan 2017 (actual)
- Primary completion
- 31 May 2017 (actual)
- Study completion
- 31 May 2017 (actual)
- First posted
- 22 Jun 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Graves orbitopathy (GO) is an inflammatory eye disease associated in 95% of patients with Graves' hyperthyroidism (GH), in ~3-4% with hypothyroid autoimmune thyroiditis, and in ~1-2% with thyroid autoimmunity in the absence of thyroid dysfunction, the former known as euthyroid GO. The pathogenesis of GO is autoimmune, with the TSH-receptor being considered the major autoantigen, thereby establishing a pathogenetic link between the thyroid and orbital tissue. Thus, TSH-receptor is expressed by orbital fibroblasts, where it forms a complex with the IGF-1 receptor. Unlike GH, which is notoriously caused by TSH-receptor stimulating autoantibodies, GO is believed to reflect cell-mediated autoimmunity, as suggested by studies showing a Th1-like pattern of cytokine release by primary cultures of orbital infiltrating lymphocytes from GO patients. On the other hand, a role of B lymphocytes has emerged in recent years based on the observation that the anti-CD20 monoclonal antibody rituximab has a beneficial effect on GO activity, as demonstrated by a recent randomized clinical trial in which rituximab was compared with intravenous glucocorticoids (GC), being the former the standard treatment of moderately-severe GO. The explanation for the findings was that B lymphocytes are involved in the pathogenesis of GO as antigen-presenting cells. However, in spite of the above mentioned promising observations, another randomized clinical trial in which rituximab was compared with placebo provided opposite results. Thus, rituximab had no effect at all on GO. Data from the two studies were confronted and major differences between the two cohorts emerged, especially concerning GO activity, leading to the conclusion that rituximab may be effective for active, but not for inactive GO. Rituximab has been employed also for autoimmune diseases other than GO, including type 1 diabetes. In the former, it was shown that the effectiveness of rituximab paralleled the presence of CD20-positive infiltrating lymphocytes in pancreas islets. We therefore postulated that something similar may occur in GO, because of which we planned the present, perspective, observational study, aimed at determining the presence and immunohistochemical features of lymphocytes infiltrating orbital tissues in patients with GO and to relate them with the clinical features of GO.
Study design
- Observational model
- Case only
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Graves' Orbitopathy | – | Other: No interventionPatients with Graves' Orbitopathy subjected to orbital decompression |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Consecutive patients with Graves' orbitopathy to undergo orbital decompression
Key inclusion criteria (1 listed)
- Patients with Graves' orbitopathy subjected to orbital decompression
Key exclusion criteria (1 listed)
- None
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| No interventionNo intervention related to the study is foreseen | Other | Graves' Orbitopathy |
Primary outcome
Correlation between lymphocytes infiltrating orbital tissue and GO activity
Time frame: an average of 1 week
Correlation between the number of lymphocytes infiltrating orbital tissues and the clinical activity score. The number of infiltrating lymphocytes is the sum of the number counted in four representative fields. The clinical activity score comprises 7 items (eyelid edema, conjuctival redness, eyelid redness, chemosis, caruncle edema, spontaneous eye pain, gaze-evoked eye pain), resulting in a numerical score going from 1 to 7
2 secondary outcomes
Correlation between CD3-positive lymphocytes infiltrating orbital tissue and GO activity
Time frame: an average of 1 week
Correlation between CD20-positive lymphocytes infiltrating orbital tissue and GO activity
Time frame: an average of 1 week
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Feb 2018.
- Individual participant dataSharing planned: No
Related trials for Graves Ophthalmopathy
Active, not recruitingPhase 4
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NEXUS Study: A Study to Test Single and Multiple Doses of MER511 Given to Adults With Graves' Disease
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Michele Marinò, MD principal investigator
University of Pisa
Questions about this trial
What is this clinical trial studying?
An observational study of Graves Ophthalmopathy, run by University of Pisa.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 12 Feb 2018. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Correlation between lymphocytes infiltrating orbital tissue and GO activity (time frame: an average of 1 week). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Feb 2018.